Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01 Naitou, K., Mamerto, T.P., Pustovit, R.V., Callaghan, B., Rivera, L.R., Chan, A.J., Ringuet, M.T., Pietra, C. and Furness, J.B. 2015, Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01, Neurogastroenterology & motility, vol. 27, no. 12, pp. 1764-1771, doi: 10.1111/nmo.12688. Attached Files Name Description MIMEType Size Downloads Title Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01 Author(s) Naitou, K. Mamerto, T.P. Pustovit, R.V. Callaghan, B. Rivera, L.R. orcid.org/0000-0002-8334-4479 Chan, A.J. Ringuet, M.T. Pietra, C. Furness, J.B. Journal name Neurogastroenterology & motility Volume number 27 Issue number 12 Start page 1764 End page 1771 Total pages 8 Publisher Wiley-Blackwell Place of publication Chichester, Eng. Publication date 2015-12 ISSN 1350-1925 Keyword(s) defecation ghrelin ghrelin receptors Summary Background It has been recently demonstrated that the ghrelin receptor agonist, HM01, caused defecation in rats that were treated to provide a model for the constipation of Parkinson's disease. HM01 significantly increased fecal output and increased Fos activity in neurons of the hypothalamus and hindbrain, but not in the spinal defecation center. Other ghrelin agonists act on the defecation center. Methods Receptor pharmacology was examined in ghrelin receptor (GHSR1a) transfected cells. Anesthetized rats were used to investigate sites and mechanisms of action. Key Results HM01 activated rat GHSR1a at nanomolar concentrations and was antagonized by the GHSR1a antagonist, YIL781. HM01, intravenous, was potent to activate propulsive colorectal contractions. This was prevented by pelvic nerve section and by intravenous YIL781, but not by spinal cord section rostral to the defecation centers. Direct intrathecal application of HM01 to the defecation center at spinal level L6-S1 initiated propulsive contractions of the colorectum. Conclusions & Inferences HM01 stimulates GHSR1a receptors on neurons in the lumbosacral defecation centers to cause propulsive contractions and emptying of the colorectum. It has greater potency when given systemically, compared with other GHSR1a agonists. Language eng DOI 10.1111/nmo.12688 Field of Research 110399 Clinical Sciences not elsewhere classified 1103 Clinical Sciences 1109 Neurosciences Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences HERDC Research category C1.1 Refereed article in a scholarly journal ERA Research output type C Journal article Grant ID NHMRC 1005811 Copyright notice ©2015, John Wiley & Sons Persistent URL http://hdl.handle.net/10536/DRO/DU:30079260 Document type: Journal Article Collections: Faculty of Health School of Medicine Related Links Link Description Connect to Elements publication management system Go to link with your DU access privileges   Connect to published version Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Tue, 03 Nov 2015, 12:51:02 EST Mon, 18 Jul 2016, 14:18:04 EST Mon, 18 Jul 2016, 15:03:22 EST Tue, 19 Jul 2016, 06:11:41 EST Tue, 19 Jul 2016, 09:57:07 EST Tue, 19 Jul 2016, 09:58:11 EST Wed, 12 Oct 2016, 14:14:26 EST Wed, 01 Mar 2017, 07:25:54 EST Sat, 17 Jun 2017, 02:38:07 EST Wed, 07 Feb 2018, 10:23:47 EST Filtered Full Citation counts:   Cited 14 times in TR Web of Science Cited 18 times in Scopus Search Google Scholar Access Statistics: 501 Abstract Views, 3 File Downloads  -  Detailed Statistics Created: Mon, 18 Jul 2016, 14:18:04 EST